Removable Covering for Implantable Frame Projections

ABSTRACT

The disclosure relates to medical devices for implantation in a body vessel, and methods of using and making the same. A medical device can include a frame with one or more projections each having at least one edge extending from the surface of the frame, and a biocompatible, water-soluble removable material coated over at least a portion of the at least one edge. The projections can be barbs positioned to engage the interior wall of a body vessel or to attach a material, such as a valve leaflet or graft, to the frame. The removable material can be dissolved within a body vessel upon implantation, thereby exposing the at least one edge. Methods of making an implantable medical device and methods of treating a subject are also disclosed.

PRIORITY CLAIM

This application is a continuation of U.S. patent application Ser. No.11/583,395, filed Oct. 19, 2006, which claims the benefit of provisionalU.S. Patent Application Ser. No. 60/729,559, filed Oct. 24, 2005, bothof which are incorporated herein by reference in their entirety.

TECHNICAL FIELD

The present disclosure relates to medical devices. More particularly,the disclosure relates to medical devices for implantation in a bodyvessel comprising frame projections covered by a removable material.

BACKGROUND

Various implantable medical devices can be deployed within the lumen ofa body vessel using minimally-invasive transcatheter techniques. Forexample, implantable medical devices can function as a replacementvalve, or restore native valve function. Such devices can include anexpandable frame configured for implantation in the lumen of a bodyvessel, such as a vein. Implantable valves can further comprise featuresthat provide a valve function, such as opposable leaflets.

Many implantable medical devices include an implantable frame having aplurality of projections extending from the surface of the frame, suchas barbs or cutting edges. The projections can have one or more sharpbeveled edges that can perform beneficial functions upon implantationwithin a body vessel, such as retaining a valve leaflet or graftmaterial attached to the medical device or securing the medical devicewithin a body vessel by puncturing and engaging the interior surface ofa body vessel. Before implantation within the body vessel, however,projections having one or more beveled edges can inadvertently andundesirably contact and even damage other portions of the medicaldevice, a delivery system or the body vessel.

There exists a need in the art for an implantable medical deviceincluding a removable material to form a protective covering over oraround one or more edges of a projection from a medical device frame.Removable materials that dissolve readily on implantation within a bodyvessel but retain a desired level of durability prior to implantationare particularly desirable. For example, a removable material can becoated over a barb extending from an implantable frame, and thendissolved rapidly upon implantation in a body vessel.

SUMMARY

The disclosure relates to removable coverings for sharp edges of animplantable medical device frame, such as a barb or other sharp frameprojection, prior to implantation of the frame in a body vessel. Animplantable frame can be an expandable stent or a portion of aprosthetic valve. The removable covering is preferably a biocompatiblewater-soluble material positioned over a sharp edge of a projectionextending from the surface of the implantable frame. The removablematerial can form a coating over the surface of the frame, or anyportion thereof that includes one or more sharp edges. The projectioncan have any desired function, but is preferably adapted to engage theinterior surface of a body vessel (such as a barb) or to retain amaterial attached to the frame (such as a valve leaflet). Theimplantable frame is preferably expandable from a compressed state fordelivery via transcatheter implantation and a radially expanded statefor deployment from a catheter within a body vessel.

Desirably, the removable material can protect the interior of the bodyvessel, material attached to the implantable frame such as valveleaflets, or portions of the delivery system from potentially damaginginadvertent contact with a sharp edge of a frame prior to and duringdeployment of the frame in a body vessel. The removable material ispreferably a water-soluble material with sufficient durability to covera sharp edge during delivery and placement within the body vessel. Theremovable material preferably has a sufficient solubility within a bodyvessel for the removable material to dissolve rapidly enough during atranscatheter delivery procedure to expose the sharp edge duringdeployment of the implantable frame prior to removal of a deliverycatheter. The removable material can be attached to itself or to theframe by any suitable means, including the application of tissueadhesives, cross-linkers, adhesives or natural materials such as fibrin.

The removable material preferably has a thickness sufficient to providea desirable level of durability, but thin enough to permit sufficientlyrapid dissolution of the removable material within a body vessel. Forexample, the removable material can have a thickness of between about 10μm and 1 mm. The removable material can form a coating over the entiresurface of an implantable frame, or only over portions of the frame suchas over projections or only the edges of projections from the frame.

Desirably, the removable material covers the edges of one or more barbprojections extending from surface of the implantable frame. The frameprojections can have any suitable size or cross-sectional shape. Forexample, a barb or other projection can have a substantially triangular,substantially square, substantially rectangular, substantiallyelliptical, or substantially semi-circular cross-sectional shape.Preferably, the cross-sectional area of the base of the projection isless than about 10 mm².

Preferably, the medical devices are configured as implantable valves,stent grafts or stents. Implantable valves and stent grafts can includea radially expandable frame and a material attached to the frame. In animplantable valve, the material can form one or more moveable valveleaflets for regulating the flow of fluid within a body vessel. In astent graft, a material can be attached around the outer surface of theimplantable frame. Preferably, the material is a remodelable material,such as small intestine submucosa (SIS).

In one example, a medical device is provided for implantation in a bodyvessel. The medical device preferably includes an implantable framehaving a surface that includes a plurality of projections extending fromthe surface, the plurality of projections each having at least onebeveled edge and including a first projection comprising a first bevelededge, the first projection having a cross-sectional area at theintersection of the projection and the surface that is less than about10 mm²; and a biocompatible removable material covering a first portionof the surface of the implantable frame including the first edge of thefirst projection. In one aspect, the removable material iswater-soluble. The plurality of projections may be configured as barbsconfigured to engage the wall of a body vessel. The surface may includea first surface portion covered by the removable material and having asurface area that is less than about 10 mm². The surface of theimplantable frame may also include a second portion that is not coveredby the removable material and does not include a projection. Theremovable material covering preferably has a thickness of between about1 μm and 1 mm thick. In one aspect, the implantable frame has a tubularconfiguration that is moveable from a radially compressed state to aradially expanded state. The implantable frame can be made from anysuitable material, but preferably includes a material selected from thegroup consisting of: a nickel-titanium alloy, a cobalt-chromium alloy,and stainless steel. Desirably, the medical device is an implantablevalve further comprising at least one valve leaflet attached to theimplantable frame, the implantable frame comprising a plurality ofstruts and bends defining a substantially cylindrical lumen and having aplurality of projections configured as barbs attached to the implantableframe.

In another example, a method of making an implantable medical devicecomprises providing a frame having one or more projections with at leastone sharp edge. The method may also comprise the step of applying aremovable material to the at least one sharp edge at a desiredthickness.

In yet another example, a method of treating a subject comprisesimplanting a medical device at a point of treatment, where the medicaldevice comprises a frame and a removable material coated over at leastone sharp edge of a projection from the frame.

Other systems, methods, features and advantages will be, or will become,apparent to one with skill in the art upon examination of the followingfigures and detailed description. It is intended that all suchadditional systems, methods, features and advantages be included withinthis description, be within the scope of the disclosure, and beprotected by the following claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The medical device may be better understood with reference to thefollowing drawings and description. The components in the figures arenot necessarily to scale, emphasis instead being placed uponillustrating the principles of the disclosure. Moreover, in the figures,like referenced numerals designate corresponding parts throughout thedifferent views.

FIG. 1 is a perspective view of a first implantable medical deviceincluding a plurality of barb projections covered with a removablematerial;

FIG. 2A is side view of a covered barb projection from the implantableframe of the first medical device shown in FIG. 1.

FIG. 2B is a cross-sectional view of the covered barb projection fromthe implantable frame of the first medical device shown in FIG. 1 andFIG. 2A.

FIG. 3 is a side view of a segment of an implantable frame portion of asecond medical device having a covering of a removable material.

FIG. 4 is a flat plan view of an implantable frame of a third medicaldevice having a removable material attached to a portion of the frame.

FIG. 5 is detailed view of a portion of the implantable frame of thethird medical device, also depicted in FIG. 4.

FIG. 6 is a perspective view of a fourth medical device including aplurality of projections covered by a removable material.

FIG. 7 is a schematic of a transcatheter delivery system for anintraluminally implantable medical device.

FIG. 8 is a diagram of a human leg showing certain venous structurestherein.

DETAILED DESCRIPTION

The following detailed description and appended drawings describe andillustrate various examples of the present disclosure. The disclosureprovides medical devices for implantation in a body vessel, methods ofmaking the medical devices, and methods of treatment that utilize themedical devices. More specifically, the disclosure relates to a medicaldevice comprising a removable material contacting at least one edge ofan implantable frame. The edge is preferably a beveled edge formed bythe intersection of at least two planar surfaces of a projection fromthe surface at an angle other than 90-degrees with respect to oneanother. Preferably, the beveled edge is a sharpened edge adapted toengage the wall of a body vessel.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this disclosure pertains. In case of conflict, thepresent document, including definitions, will control. Preferred methodsand materials are described below, although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present disclosure. All publications, patentapplications, patents and other references mentioned herein areincorporated by reference in their entirety. The materials, methods, andexamples disclosed herein are illustrative only and not intended to belimiting.

DEFINITIONS

As used herein the terms “comprise(s),” “include(s),” “having,” “has,”“contain(s),” and variants thereof, are intended to be open-endedtransitional phrases, terms, or words that do not preclude thepossibility of additional acts or structure.

As used herein, the term “body vessel” means any tube-shaped bodypassage lumen that conducts fluid, including but not limited to bloodvessels such as those of the human vasculature system, biliary ducts andureteral passages.

As used herein, the term “implantable” refers to an ability of a medicaldevice to be positioned at a location within a body, such as within abody vessel. Furthermore, the terms “implantation” and “implanted” referto the positioning of a medical device at a location within a body, suchas within a body vessel.

As used herein, “endolumenally,” “intraluminally” or “transluminal” allrefer synonymously to implantation placement by procedures where themedical device is advanced within and through the lumen of a body vesselfrom a remote location to a target site within the body vessel. Invascular procedures, a medical device will typically be introduced“endovascularly” using a catheter over a guidewire under fluoroscopicguidance. The catheters and guidewires may be introduced throughconventional access sites to the vascular system, such as through thefemoral artery, or brachial and subclavian arteries, for access to thecoronary arteries.

A “biocompatible” material is a material that is compatible with livingtissue or a living system in a manner consistent with an intendedtreatment, for example by not being toxic or injurious to an undesirableextent, or not causing undesirable levels of immunological rejection.

The term “frame” refers to any biocompatible frame suitable forimplantation within a body vessel. Preferably, a frame can expand from aradially compressed, or unexpanded, delivery configuration to one ormore radially expanded deployment configurations, for example throughself-expansion or balloon expansion of the frame. The expandedconfiguration can have any suitable cross-sectional configuration,including circular or elliptical. In one example, the frame can beoriented along the longitudinal axis of a body vessel in the expanded orcompressed configurations.

As used herein, a “point of attachment” refers to a location where twoadjacent surfaces are joined together.

The terms “remodelable” or “bioremodelable” refer to the ability of amaterial to allow or induce host tissue growth, proliferation orregeneration following implantation of the tissue in vivo. Remodelingcan occur in various microenvironments within a body, including withoutlimitation soft tissue, a sphincter muscle region, body wall, tendon,ligament, bone and cardiovascular tissues. Upon implantation of aremodelable material, cellular infiltration and neovascularization on orwithin the remodelable material are typically observed over a period ofabout five days to about six months or longer, as the remodelablematerial acts as a matrix for the ingrowth of adjacent tissue withsite-specific structural and functional properties. The remodelingphenomenon which occurs in mammals following implantation of submucosaltissue typically includes rapid neovascularization and early mononuclearcell accumulation. Mesenchymal and epithelial cell proliferation anddifferentiation are typically observed by one week after in vivoimplantation and extensive deposition of new extracellular matrix occursalmost immediately. In some examples, fluid contacting autologous cellson an implanted remodelable material can affect the growth of autologoustissue on the implanted remodelable material.

Medical Device Configurations

FIG. 1 is a perspective view of an implantable medical device includinga plurality of barb projections covered with a removable material. Themedical device 10 is a valve including a radially expandable frame 20shown in a radially expanded state within a segment of a body vessel 40,and a pair of valve leaflets 60, 62 attached to the frame 20. The outersurface of the frame 25 contacting the body vessel 40 can include aplurality of projections 30 configured as barbs that extend from theframe 20 and are configured to engage the wall of the body vessel 40.Each projection 30 includes a sharp beveled edge and is covered by aremovable covering before implantation in the body vessel 40. The frame20 can be formed from a self-expanding material, such as a superelasticnickel-titanium alloy, that exerts an outward radial force against thebody vessel 40. The frame 20 is delivered in a radially compressed stateby a delivery catheter and permitted to expand by self-expansion at thepoint of treatment. The projections 30 are configured to engage theinterior wall of a body vessel 40 to secure the frame 20 and preventmigration of the implant. The projections can have any suitable size orcross-sectional shape. For example, a barb or other projection can havea substantially triangular, substantially square, substantiallyrectangular, substantially elliptical, or substantially semi-circularcross-sectional shape. Preferably, the cross-sectional area of the baseof the projection is less than about 10 mm², preferably about 0.1-1 mm².Each side of the base of the projection can be, for example, about0.01-10 mm, but is preferably about 0.5-2 mm on each side. Suitablecross-sectional areas of a barb projection can be on the order of 0.1-10mm², preferably about 0.5-5 mm², and more preferably about 1 mm².

The medical device 10 includes a plurality of interconnected struts 21and bends 23, and includes a serpentine ring segment or hoop member 22at the distal end and a “double-V” shaped proximal frame portion 24. Apair of valve leaflets 60, 62 are attached to a first pair of struts 27a and a second pair of struts 27 b. The distal end of the pair of valveleaflets 60, 62 are opposably positioned to define a valve orifice 64that has an open position and a closed position. The valve orifice opensto permit fluid to flow from the proximal end 2 of the medical device 10to the distal end 4, and closes to substantially prevent fluid flow inthe opposite direction. The valve leaflets 60, 62 can be formed from amaterial that is flexible enough to move the valve orifice between theopen and closed positions in response to changes of fluid flow orpressure within the medical device 10. Examples of suitable valvematerial include extracellular matrix materials (ECM) such as smallintestine submucosa and biostable polymer materials such as PTFE andePTFE.

FIG. 2A is side view of a covered barb projection from the implantableframe in FIG. 1. FIG. 2A shows frame segment 12, a cross section alongthe line A-A′ in FIG. 1 of the frame 20, which includes a projection 32.The projection 32 includes a first sharp beveled edge 34 and a secondsharp beveled edge 36 meeting in a point. The projection 32 is coveredby a rounded removable material 52. Alternatively, the removablematerial 52 can be positioned adjacent to, rather than covering, aprojection 30. For example, a removable material can be depositedadjacent to a projection 30 on the outer surface 25 of the frame, andcan extend farther from the frame surface than the projection 30. Theouter surface 25 of the frame segment 12 includes an uncovered portion26 that is not coated with the removable material 52 and a coveredportion 29 that is covered with the removable material. Alternatively,the covered portion 29 of the frame segment 12 can be positionedadjacent to the projection 32, while the uncovered portion 26 caninclude the barb projection 32. FIG. 2B is a cross-sectional view of thecovered barb projection 32 from the implantable frame 12 along the lineB-B′ in FIG. 2A. FIG. 2B shows frame segment 12, along the cross sectionline B-B′ in FIG. 2A of the frame segment barb projection 32, whichincludes a projection 32. The projection 32 is covered by a removablematerial 52. The outer surface 25 of the frame segment 12 includes anuncovered portion 26 that is not coated with the removable material 52and a covered portion 29 that is covered with the removable material.

FIG. 3 is a longitudinal cross sectional view of a segment of a secondimplantable frame having a covering of a removable material. The segment110 of the implantable frame 120 comprises a plurality of interconnectedstruts 122 and bends 124. The frame 120 also includes a plurality ofbarbs 130 extending from certain bends. A coating layer 150 of removablematerial 152 covers one surface of the frame segment, enclosing thebarbs 130. Upon implantation in a body vessel, the coating layer 150 canbe rapidly dissolved by exposure to bodily fluids, exposing the barbs130. Alternatively, the coating layer 150 can be thicker than the heightof the barbs 130, and can be positioned intermittently to cover portionsof the frame between the barbs 130, while leaving the barbs exposed 130.In this manner, the coating 150 can be configured to protect tissue fromcontacting the barbs 130 prior to removal of the removable material 152.

FIG. 4 is a flat plan view of a third implantable frame having aremovable material attached to a portion of the frame. The implantableframe 210 is formed when the C-C′ line is placed coincident to the D-D′line, to form a tubular frame defining a cylindrical central lumen. Theframe 210 includes a plurality of interconnected struts 220 and bends222, and includes a plurality of barbs 230 attached to certain bends222. The plurality of barbs 230, including a first barb 231, are coveredby a removable material 252 that dissolves upon contact with fluidwithin a body vessel as the frame 210 is being implanted therein. Aportion 212 of the implantable frame 210 is shown in FIG. 5. FIG. 5 is adetailed view of a portion of the frame 210 including the first barb231. The barb 231 projects from the frame 210 and includes a first edge232 and a second edge 234. The barb 230 is enclosed in the removablematerial 252.

FIG. 6 is a perspective view of a fourth implantable frame 260 in aradially expanded state comprising a plurality of sharpened projections280 covered by a removable material 282. The sharpened projections 280are configured to engage the wall of a body vessel upon expansion of theframe 260 and after dissolution of the removable material 282 within abody vessel. Alternative examples include any implantable medical devicehaving a portion of the surface, such as a sharp beveled edge of avalvulotome that can be covered with a removable material beforedeployment within a body vessel.

Removable Material

A variety of removable materials may be used to cover an implantableframe projection. Preferably the removable material is durable, solid,and flexible at room temperature, and dissolves readily when exposed toblood under normal blood temperatures and pH. The rate of dissolution ofthe removable materials can be varied by changing the molecular weightsof the removable material. Typically, the lower the molecular weight ofa removable material polymer, the faster the removable material willdissolve. The molecular weight of the polymer can be selected to providea desired rate of dissolution and durability. Some polymers, such aschondroitin sulfate, may occur in nature with a molecular weight as highas 25,000, while others, such as hydroxypropylmethyl cellulose might beas high as 1,000,000. Hyaluronate may have a molecular weight as greatas 8,000,000. Preferably, the removable material is a water-solublepolymer that it rapidly imbibes water and softens and/or dissolveswithin a aqueous substance. The molecular weight of the polymer shouldbe high enough so that the wet polymer has enough strength and filmintegrity remain intact during delivery of the medical device through abody vessel, and low enough so that the removable material will dissolverapidly during deployment of the medical device. Varying the thicknessor adding perforations will also increase the rate of dissolution of theremovable material materials.

In a first aspect, the removable material comprises cellulose or acellulose-based material. Suitable cellulosic polymers include:microcrystalline cellulose, cellulose alkyl ethers, carboxymethylcellulose, and cellulose alkyl esters. Preferred cellulose alkyl ethersinclude: methylcellulose, ethyl cellulose, hydroxymethyl cellulose,hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethylcellulose, hydroxypropyl methyl cellulose (MPMC) and carboxymethylcellulose. Preferred cellulose alkyl esters include: celluloseacetophthalate, cellulose acetate, cellulose acetate phthalate (CAP),hydroxypropyl methylcellulose phthalate (HPMCP), hydroxyethyl cellulose,and hydroxypropyl methylcellulose acetate succinate (HPMCAS). Othernaturally occurring polymers, such as chondroitin sulfate, may also beused as a removable material. Still other suitable removable materialmaterials are the water-soluble cellulose mixed ethers disclosed in U.S.Pat. No. 4,358,587 to Brandt et al., incorporated herein by reference.

In a second aspect, the removable material comprises a suitable vinylpolymer, such as polyvinylpyrolidone (PVP), polyvinyl alcohol (PVA),crosslinked PVP, PVA or PVA/PVP co-polymers. The removable material mayalso include a polyacrylamide, a poly(methylvinyl ether), or polyacrylicacid.

In a third aspect, the removable material may also include a polymercomprising polyethylene or polyacrylic acid. For example, the removablematerial is preferably a polyethyleneoxide or poly(ethylene glycol)(PEG), having a weight average molecular weight in the range from 1000to about 10,000 (preferably 8000). The removable material may alsoinclude the removable material comprises one or more esters ofpoly(meth)acrylic acid where the ester group may be represented by theformula —OR in which the R moiety is sufficiently small (e.g., methyl orethyl or other C1 or C2 type of moiety) so that the polymer is watersoluble; similar esters of polyvinyl alcohol; combinations of these, andthe like. Most preferably, the water soluble material is PEG, morepreferably PEG having a weight average molecular weight of about 8000.Hyaluronate may also be used as a removable material.

In a fourth aspect, the removable material may comprise a carbohydrateor starch, such as mannitol, pullulan (.alpha.-1,4-;.alpha.-1,6-glucan),chitin, chitosan, polysaccharides such as pectin and elsinan, orstarches and modified starches such as maltodextrin, amylose, highamylose starch, hydroxypropylated high amylase starch, acid and enzymehydrolyzed corn and potato starches.

In a fifth aspect, the removable material may include suitable naturalgums such as gum arabic, guar gum, locust bean gum, carrageenan gum,acacia, karaya, ghatti, tragacanth agar, tamarind gum, and xanthan gum.The removable material may also include gelatins, seaweed extracts suchalginates (propylene glycol alginate, sodium alginate and the like),carrageenans or plant extracts such as konjac, pectin orarabinogalactan.

In a sixth aspect, the removable material can be applied to a portion ofthe medical device that is modified to permit attachment of theremovable material. Preferably, projections from the surface of themedical device that include a beveled edge can be treated to permitadhesion of a removable material. In particular, beveled edges can beplasma pre-treated and coated with an amine-containing material, towhich a water soluble polymer can be attached. For example, the plasmatreated surface may be coated with a material containing amine groups,such as polyethyleneimine (PEI). Alternatively, a beveled edge of aprojection from the surface of the medical device can be treated with ahighly adherent material, such as acrylic acid polymers or copolymers,to promote the adherence of the amine groups to the substrate.Subsequently, the treated surface can be contacted with an aldonic acidand a coupling agent, such as a water-soluble carbodiimide. Onepreferred water-soluble carbodiimide is1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). The pH of themixture is adjusted until the pH stabilizes. Then the mixture is broughtinto contact with the substrate, at room temperature. Components of thealdonic acid and the coupling agent may be reacted with the amine groupson the coating over the beveled edges, such that the beveled edgesbecome coated with aldonic acid amide. The components which do not formpart of the aldonic acid amide can be washed away and discarded. Otherexamples of aldonic acid-amine coatings are disclosed in U.S. Pat. No.6,187,369 (Beavers).

Additives may also be added to affect desired properties of theremovable material. For example, plasticizers are known in the art toincrease flexibility when added to the removable material. Plasticizersinclude glycerol, sorbitol, polyethylene glycol, polypropylene glycol orsugars (glucose, maltodextrins, acetylated monoglycerides, citric orlactic acid esters). Brittleness may be reduced by adding esters offatty acids and glycerol, examples of which include: glycerol monofattyacid esters, glycerol acetate fatty acid esters, glycerol lactate fattyacid esters, glycerol citrate fatty acid esters, glycerol succinatefatty acid esters, glycerol diacetyltartrate fatty acid esters andglycerol monoacetate. Other derivatives of the monoglyceride reactedwith acetic acid, lactic acid, citric acid, succinic acid ordiacetyltartaric acid may also be included in the ester of a fatty acidand glycerol.

Valve Leaflet or Graft Materials

A variety of materials can be attached to an implantable frame, forexample to form a valve leaflet or a stent graft, including naturallyderived materials, and synthetic materials.

In one aspect, the medical device includes a remodelable materialattached to a frame. Preferably, the implantable medical device includesa valve leaflet or graft material comprising a remodelable material.Examples of suitable natural materials include remodelable materials,such as collagen and extracellular matrix (ECM) material. Smallintestine submucosa (SIS) is particularly well-suited as a material,such as to form valve leaflets. Submucosal tissue can be obtained fromwarm-blooded tissues including the alimentary, respiratory, intestinal,urinary or genital tracts of warm-blooded vertebrates, including withoutlimitation: intestinal submucosa, stomach submucosa, urinary bladdersubmucosa, and uterine submucosa. Other examples of ECMs arepericardium, stomach submucosa, liver basement membrane, urinary bladdersubmucosa, tissue mucosa, and dura mater. Information as to submucosamaterials useful as ECM materials herein can be found in U.S. Pat. Nos.4,902,508; 5,554,389; 5,993,844; 6,206,931; 6,099,567; and 6,375,989, aswell as published U.S. Patent Applications US2004/0180042A1 andUS2004/0137042A1, which are all incorporated herein by reference. Forexample, the mucosa can also be derived from vertebrate liver tissue asdescribed in WIPO Publication, WO 98/25637, based on PCT applicationPCT/US97/22727; from gastric mucosa as described in WIPO Publication, WO98/26291, based on PCT application PCT/US97/22729; from stomach mucosaas described in WIPO Publication, WO 98/25636, based on PCT applicationPCT/US97/23010; or from urinary bladder mucosa as described in U.S. Pat.No. 5,554,389; the disclosures of all are expressly incorporated herein.

Preferably, the source tissue for the ECM material is a submucosaltissue, such as tela submucosa, that is disinfected prior todelamination by the preparation disclosed in US Patent ApplicationUS2004/0180042A1 by Cook et al., published Sep. 16, 2004 andincorporated herein by reference in its entirety. Most preferably, thetunica submucosa of porcine small intestine is processed in this mannerto obtain the ECM material. Other disclosures of methods for theisolation of ECM materials include the preparation of intestinalsubmucosa described in U.S. Pat. No. 4,902,508, the disclosure of whichis incorporated herein by reference. Urinary bladder submucosa and itspreparation are described in U.S. Pat. No. 5,554,389, the disclosure ofwhich is incorporated herein by reference. Stomach submucosa has alsobeen obtained and characterized using similar tissue processingtechniques, for example as described in U.S. patent application Ser. No.60/032,683 titled STOMACH SUBMUCOSA DERIVED TISSUE GRAFT, filed on Dec.10, 1996, which is also incorporated herein by reference in itsentirety.

In another aspect, the medical device includes a synthetic materialattached to a frame. The synthetic material is preferably abiocompatible polymer. For instance, the implantable medical device mayinclude a valve leaflet or graft material comprising a syntheticmaterial, or a composite material including a synthetic material and aremodelable material. Examples of suitable synthetic materials includepolymeric materials, such as polypropylene, polyurethane, expandedpolytetrafluoroethylene (ePTFE), polyurethane (PU), polyethyleneterephthalate (PET), silicone, latex, polyethylene, nylon,polytetrafluoroethylene, polyimide, polyester, and mixture thereof.

Implantable Frames

The medical device can include an implantable frame with one or moreprojections. The frame can have any suitable configuration. The specificimplantable frame chosen will depend on several considerations,including the size and configuration of the vessel and the size andnature of the medical device. The frame can perform any desiredfunction, including a stenting function or a valve support function. Theframe configuration may be selected based on several factors, includingthe vessel in which the medical device is being implanted, the axiallength of the treatment site, the inner diameter of the body vessel, andthe desired delivery method for placing the support structure. Thoseskilled in the art can determine an appropriate stent based on these andother factors. The implantable frame can be sized so that the expandedconfiguration is slightly larger in diameter that the inner diameter ofthe vessel in which the medical device will be implanted. This sizingcan facilitate anchoring of the medical device within the body vesseland maintenance of the medical device at a point of treatment followingimplantation.

Suitable implantable frames can also have a variety of configurations,including braided strands, helically wound strands, ring members,consecutively attached ring members, tube members, and frames cut fromsolid tubes. Also, suitable frames can have a variety of sizes. Theexact configuration and size chosen will depend on several factors,including the desired delivery technique, the nature of the vessel inwhich the device will be implanted, and the size of the vessel. A framestructure and configuration can be chosen to facilitate maintenance ofthe device in the vessel following implantation. The implantable framecan be formed in any suitable shape, including a ring, a stent, a tube,or a zig-zag configuration. In one example, the implantable frame can beself-expanding or balloon-expandable.

The implantable frame can be made from one or more suitable materials,including metal or polymer materials. In one aspect, the medical deviceincludes a frame comprising a biocompatible metal or metal alloy.Examples of suitable metallic materials include, without limitation:stainless steel (such as 316 stainless steel), nickel titanium (NiTi)alloys (such as Nitinol) and other shape memory and/or superelasticmaterials, MP35N, gold, silver, a cobalt-chromium alloy, tantalum,platinum or platinum iridium, or other biocompatible metals and/oralloys.

The implantable frame can be formed, from a variety of medical gradepolymers having properties that permit the frame to function as asupporting structure for the remodelable material. Suitable non-metallicframe materials include carbon or carbon fiber, cellulose acetate,cellulose nitrate, silicone, cross-linked polyvinyl alcohol (PVA)hydrogel, cross-linked PVA hydrogel foam, polyamide, styreneisobutylene-styrene block copolymer (Kraton), polyethyleneterephthalate, polyurethane, polyamide, polyester, polyorthoester,polyanhydride, polyether sulfone, polycarbonate, polypropylene, highmolecular weight polyethylene, polytetrafluoroethylene, or otherbiocompatible polymeric material, or mixture of copolymers thereof.

Optionally, the implantable frame may comprise a bioabsorbable orremodelable material. The implantable frame can comprise a bioabsorbablematerial that can be degraded and absorbed by the body over time toadvantageously eliminate a frame structure from the vessel before,during or after the remodeling process. A number of bioabsorbablehomopolymers, copolymers, or blends of bioabsorbable polymers are knownin the medical arts. These include, but are not necessarily limited to,polyesters, poly(amino acids), copoly(ether-esters), polyamides,poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters,polyoxaesters containing amido groups, poly(anhydrides),polyphosphazenes, poly-alpha-hydroxy acids, poly-beta-hydroxy acids,polyorganophosphazines, polyesteramides, polyester-ethers,polyphosphoesters, polyphosphoester urethane, cyanoacrylates,polyalkylene oxalates, polyvinylpyrolidone, polyglycols, aliphaticpolyesters, poly(ester-amides), modified polysaccharides and modifiedproteins.

Some specific examples of bioabsorbable materials include polymers andco-polymers comprising a polylactic acid, a polyglycolic acid, apolycaprolactone or derivatives thereof. Other suitable bioabsorbablematerials for a frame include: poly(trimethylene carbonate), polyvinylalcohol, poly-N-(2-hydroxypropyl)-methacrylamide, polyethylene oxide,poly(epsilon-caprolactone), poly(dimethyl glycolic acid), poly(hydroxybutyrate), polydioxanone, polyethylene oxide-polylactic acid copolymers(PEO/PLA), polylactic acid (PLA), poly(lactide-co-glycolide),poly(hydroxybutyrate-co-valerate), poly(glycolic acid-co-trimethylenecarbonate), poly(epsilon-caprolactone-co-p-dioxanone), poly-L-glutamicacid or poly-L-lysine, polyhydroxyvalerate, fibrinogen, starch,collagen, hyaluronic acid, hydroxyethyl starch, and gelatin. A frame mayalso comprise one or more naturally derived bioabsorbable polymers,including modified polysaccharides such as cellulose, chitin, anddextran or modified proteins such as fibrin and casein.

In some examples, the implantable frames impart radially outwarddirected force during deployment, whether self-expanding orradially-expandable. The radially outward directed force can serve tohold the body lumen open against a force directed radially inward, aswell as preventing restriction of the passageway through the lumen byintimal flaps or dissections generated by, such as prior balloonangioplasty. Another function of the radially outward directed force canalso fix the position of the stent within the body lumen by intimatecontact between the stent and the walls of the lumen. Preferably, theoutwardly directed forces do not traumatize the lumen walls.

Preferably, the frame is self-expanding. Upon compression,self-expanding frames can expand toward their pre-compression geometry.In some examples, a self-expanding frame can be compressed into alow-profile delivery conformation and then constrained within a deliverysystem for delivery to a point of treatment in the lumen of a bodyvessel. At the point of treatment, the self-expanding frame can bereleased and allowed to subsequently expand to another configuration. Incertain examples, the frame is formed partially or completely of alloyssuch as nitinol (NiTi) which have superelastic (SE) characteristics.However, while some examples provide frames made from shape memorymaterials, other examples comprise other materials such as stainlesssteel, MP35N and other suitable materials. Some examples provide framesthat are not self-expanding, or that do not comprise superelasticmaterials.

The frame preferably includes projections, such as barbs, that maintainthe frame in position following implantation in a body vessel. The artprovides a wide variety of structural features that are acceptable foruse in the medical device, and any suitable structural feature can beused. Furthermore, barbs can also comprise separate members attached tothe frame by suitable attachment means, such as welding and bonding. Forinstance, barbs can be formed by V-shaped cuts transversing thethickness of a flat metal frame, which are bent outward to form thebarb. In some examples, the number, arrangement, and configuration ofthe integral barbs can vary according to design preference and theclinical use of the device. The barbs can have any suitable shape,including points or “fish hook”-like configurations. The barbs may ormay not penetrate the vein wall, depending on their design and otherfactors, including the thickness and type of covering used.

Also provided are examples where the frame comprises a means fororienting the frame within a body lumen. For example, the frame cancomprise a marker, such as a radiopaque portion of the frame that wouldbe seen by remote imaging methods including X-ray, ultrasound, MagneticResonance Imaging and the like, or by detecting a signal from orcorresponding to the marker. In other examples, the delivery device cancomprise a frame with indicia relating to the orientation of the framewithin the body vessel. In other examples, indicia can be located, forexample, on a portion of a delivery catheter that can be correlated tothe location of the frame within a body vessel. A frame or deliverydevice may comprise one or more radiopaque materials to facilitatetracking and positioning of the medical device, which may be added inany fabrication method or absorbed into or sprayed onto the surface ofpart or all of the medical device. The degree of radiopacity contrastcan be altered by implant content. Radiopacity may be imparted bycovalently binding iodine to the polymer monomeric building blocks ofthe elements of the implant. Common radiopaque materials include bariumsulfate, bismuth subcarbonate, and zirconium dioxide. Other radiopaqueelements include: cadmium, tungsten, gold, tantalum, bismuth, platinum,iridium, and rhodium. In one preferred example, iodine may be employedfor its radiopacity and antimicrobial properties. Radiopacity istypically determined by fluoroscope or x-ray film. Various other ways toincorporate radiopaque material in a medical device are provided incopending application Ser. No. 10/787,307, filed Feb. 26, 2004 by Caseet al., entitled “Prosthesis Adapted for Placement Under ExternalImaging,” which is incorporated herein by reference. Imagable markers,including radiopaque material, can be incorporated in any portion of amedical device. For example, radiopaque markers can be used to identifya long axis or a short axis of a medical device within a body vessel.For instance, radiopaque material may be attached to a frame or woveninto portions of the valve member material.

Methods of Manufacturing

A method of making an implantable medical device can comprise providinga frame and covering the frame with a removable material. The removablematerials can be first mixed in liquid form, forming a solution that canbe applied to the surface of the frame in a manner permitting removal ofthe solvent and deposition of the removable material in a solid form.Solvents may be used to achieve the solution, such as water,water-dispersible polymers, tetrahydrofuran, alcohols, dichloromethane,methanol, acetone or other solvents.

The deposition of the removable material onto the surface of the framecan be performed using any conventional coating processes, for exampleimmersion or dip coating, air knife coating, spray coating or acombination thereof. For dip coating, the portion of the frame to becoated is dipped into the coating solution, and then removed. For airknife coating, the coating is applied, and the excess is “blown off” bya powerful jet from an air knife. For spray coating, the coatingsolution may be applied to the frame, barb, or portion thereof using anycommercial spray coater equipment. Spray coating equipment variables canbe manipulated by one skilled in the art to form a suitable removablematerial layer.

The thickness of the resulting removable material may depend on theconcentration of the coating solution and the number of layers ofremovable material applied. Multiple coating layers may be applied toachieve a desired thickness. The removable material preferably has athickness sufficient to provide a desirable level of durability, butthin enough to permit sufficiently rapid dissolution of the removablematerial within a body vessel. For example, the removable material canhave a thickness of between about 10 μm and 1 mm, including 10, 50, 100,250, 500, 750 and 1,000 μm (1 mm). The removable material can form acoating over the entire surface of an implantable frame, or only overportions of the frame such as over projections or only the edges ofprojections from the frame.

A drying phase may be employed after the coating is applied such as airdrying, baking, vacuum drying or dehydrating, for example, with acirculating warm gas such as air or nitrogen or other inert gas. Dryingof the solution and or coating can carried out in a high-temperatureair-bath using a drying oven, drying tunnel, vacuum drier, or any othersuitable drying equipment.

In some examples, a bioabsorbable suture or sheath can be used tomaintain a medical device in a compressed configuration both prior toand after deployment. As the bioabsorbable sheath or suture is degradedby the body after deployment, the medical device can expand within thebody vessel. In some examples, a portion of the medical device can berestrained with a bioabsorbable material and another portion allowed toexpand immediately upon implantation. For example, a self-expandingframe can be partially restrained by a bioabsorbable material upondeployment and later expand as the bioabsorbable material is absorbed.

Methods of manufacture may also comprise the step of attaching a firstvalve member to a frame. The valve member can be responsive to the flowof fluid through the frame, and adapted to permit fluid flow throughsaid vessel in a first direction or substantially prevent fluid flowthrough said vessel in a second, opposite direction. The frame can havea longitudinal axis, a first radial compressibility along a first radialdirection that is less than a second radial compressibility along asecond radial direction.

Percutaneous Delivery of Medical Devices

In some examples, the medical devices can be configured for delivery toa body vessel. Preferably, the medical device is implanted in a radiallycompressed configuration, and radially expanded at a point of treatmentwithin a body vessel. The overall configuration, cross-sectional area,and length of a medical device frame having a tubular configuration(compressed or expanded) may depend on several factors, including thesize and configuration of device, the size and configuration of thevessel in which the device will be implanted, the extent of contactbetween the device and the walls of the vessel, and the amount ofretrograde flow through the vessel that is desired.

In some examples, implantable frames can be intraluminally deliveredinside the body by a catheter that supports the implantable frame in acompacted form as it is transported to the desired site, for examplewithin a body vessel. Upon reaching the site, the implantable frame canbe expanded and securably placed within the body vessel, for example bysecurably engaging the walls of the body vessel lumen. The expansionmechanism may involve forcing the stent to expand radially outward, forexample, by inflation of a balloon formed in the distal portion of thecatheter, to inelastically deform the stent and fix it at apredetermined expanded position in contact with the lumen wall. Theexpansion balloon can then be deflated and the catheter removed. Inanother technique, the implantable frame is formed of a material thatwill self-expand after being compacted. During introduction into thebody, the implantable frame is restrained in the compacted condition.When the stent has been delivered to the desired site for implantation,the restraint is removed, allowing the implantable frame to self-expandby its own internal elastic restoring force. Once the implantable frameis located at the constricted portion of the lumen, the sheath isremoved to expose the stent, which is expanded so it contacts the lumenwall. The catheter is subsequently removed from the body by pulling itin the proximal direction, through the larger lumen diameter created bythe expanded prosthesis, which is left in the body.

FIG. 7 is a schematic of a transcatheter delivery system for anintraluminally implantable medical device. The medical device mayinclude an implantable frame designed to be percutaneously deliveredthrough a body lumen to a target site. The target site may be, forexample, a location in the venous system adjacent to an insufficientvenous valve. The implantable frames may be delivered, for example, ontheir own or as part of an implantable prosthetic valve. FIG. 7illustrates a delivery system 300. The delivery system 300 includes acatheter 310 having a distal end 314. A balloon 320 is positioned on thedistal end 314 of the catheter 310. A connector assembly 330 is disposedat the proximal end 335 of the catheter 310 and is adapted to facilitateexpansion of the balloon 320 as is known in the art. The connectorassembly 330 provides access to an interior lumen of the catheter 310 toprovide access to the balloon 320, and possibly a guidewire (notillustrated) or other conventional component. A balloon expandable frame350 according to the present disclosure is disposed on the distal end314 of the catheter 310. The expandable frame 350 surrounds the balloon320 and is initially, prior to placement in a body vessel, in itsunexpanded state. This positioning allows the balloon 320, uponinflation, to radially expand the expandable frame 350 into its expandedstate. Alternatively, a self-expanding medical device frame can becompressed to a delivery configuration within a retaining sheath that ispart of a catheter delivery system. Upon delivery, the radiallycompressed configuration can be expanded, for example, by removing aself-expanding frame, or portion thereof, from the sheath or byinflating a balloon from inside the medical device. The frame can bemaintained in the radially compressed configuration prior to deploymentof the medical device by any suitable means, including a sheath, asuture, a tube or other restraining material around all or part of thecompressed medical device, or other methods.

As indicated above, the present disclosure is well-suited for providingartificial support to a body vessel in need of such support. This can beperformed by inserting the distal end 314 of the catheter 310 into abody vessel and navigating the distal end 314, and the surroundingexpandable frame 350, to a point in a vessel in need of radial support.The catheter 310 can be placed over a guidewire (not illustrated) tofacilitate navigation. Once the expandable frame 350 is at the point oftreatment, the balloon 320 can be inflated in the conventional manner.Inflation of the balloon 320 forces the expandable frame 350 to expand.During expansion, in which the expandable frame 350 changes from aradially compressed state to a radially expanded state. Followingexpansion, the balloon 320 can be deflated, leaving the expandable frame350 in its expanded state. The catheter 310 can then be withdrawn fromthe vessel, leaving the expandable frame 350 in its expanded state atthe point of treatment within the body vessel.

Implantable frames or prostheses comprising the implantable frame can bedelivered into a body lumen using a system which includes a catheter. Anappropriately sized delivery catheter can be selected by one skilled inthe art for a given application. For example, some examples can bedelivered using a delivery catheter selected from one or more deliverycatheter sizes from the group consisting of: 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27,28, 29 and 30 French (F) delivery catheters, or increments of 0.1 Ftherebetween. In some examples, a delivery catheter sized between 1 and25 F, or preferably between about 1.5 F and 5 F can be used, preferablya 1.8 F (0.60 mm), 2.0 F (0.66 mm), 2.3 F (0.75 mm), 2.6 F (0.85 mm),2.7 F (0.9 mm), 2.9 F (0.95 mm), or 3.3 (1.10 mm) delivery catheters.

The implantable frames can be placed in any medically appropriatelocation for a given application. For example, in some examples, theimplantable frame can serve as part of a venous valve prosthetic and beimplanted in the femoral vein, including at the proximal (groin), mid(mid section) or distal (adjacent to the knee) portions of the vein.

Methods of Treatment

Also provided are methods of treating a patient. In one example themethod comprises a step of delivering a medical device as describedherein to a point of treatment in a body vessel, and deploying themedical device at the point of treatment. Additionally, the medicaldevice can comprise a frame and a removable material.

Methods for treating certain conditions are also provided, such asvenous valve insufficiency, varicose veins, esophageal reflux,restenosis or atherosclerosis. In some aspects, the disclosure relatesto methods of treating venous valve related conditions. A “venous valverelated condition” is any condition presenting symptoms that can bediagnostically associated with improper function of one or more venousvalves. In mammalian veins, natural valves are positioned along thelength of the vessel in the form of leaflets disposed annularly alongthe inside wall of the vein which open to permit blood flow toward theheart and close to prevent back flow. These natural venous valves act asopen to permit the flow of fluid in the desired direction, and closeupon a change in pressure, such as a transition from systole todiastole. When blood flows through the vein, the pressure forces thevalve leaflets apart as they flex in the direction of blood flow andmove towards the inside wall of the vessel, creating an openingtherebetween for blood flow. Functioning leaflets return to a closedposition to restrict or prevent blood flow in the opposite, i.e.retrograde, direction after the pressure is relieved. The leaflets, whenfunctioning properly, extend radially inwardly toward one another suchthat the tips contact each other to block backflow of blood. Twoexamples of venous valve related conditions are chronic venousinsufficiency and varicose veins.

On occasion, and for a variety of reasons, such as congenital valve orvein weakness, disease in the vein, obesity, pregnancy, and/or anoccupation requiring long periods of standing, one or more valves in avein will allow deleterious retrograde flow to occur. When a valveallows such retrograde flow, blood will collect, or pool in vesselsbeneath the valve. This pooling of blood causes an increase in thevenous pressure below the valve. Venous valves that allow suchdeleterious retrograde flow are known as incompetent or inadequatevenous valves. The condition resulting from such incompetent venousvalves is known as venous valve insufficiency. In the condition ofvenous valve insufficiency, the venous valve leaflets do not functionproperly. Incompetent venous valves can cause the veins to bulge, cancause swelling in the patient's lower extremities, and can result invaricose veins and/or chronic venous insufficiency. If left untreated,venous valve insufficiency can cause venous stasis ulcers of the skinand subcutaneous tissue.

In the condition of venous valve insufficiency, the valve leaflets donot function properly. For example, the vein can be too large inrelation to the leaflets so that the leaflets cannot come into adequatecontact to prevent backflow (primary venous valve insufficiency), or asa result of clotting within the vein that thickens the leaflets(secondary venous valve insufficiency). Incompetent venous valves canresult in symptoms such as swelling and varicose veins, causing greatdiscomfort and pain to the patient. If left untreated, venous valveinsufficiency can result in excessive retrograde venous blood flowthrough incompetent venous valves, which can cause venous stasis ulcersof the skin and subcutaneous tissue. Venous valve insufficiency canoccur, for example, in the superficial venous system, such as thesaphenous veins in the leg, or in the deep venous system, such as thefemoral and popliteal veins extending along the back of the knee to thegroin.

The varicose vein condition consists of dilatation and tortuousity ofthe superficial veins of the lower limb and resulting cosmeticimpairment, pain and ulceration. Primary varicose veins are the resultof primary incompetence of the venous valves of the superficial venoussystem. Secondary varicose veins occur as the result of deep venoushypertension which has damaged the valves of the perforating veins, aswell as the deep venous valves. The initial defect in primary varicoseveins often involves localized incompetence of a venous valve thusallowing reflux of blood from the deep venous system to the superficialvenous system. This incompetence is traditionally thought to arise atthe saphenofemoral junction but may also start at the perforators. Thus,gross saphenofemoral valvular dysfunction may be present in even mildvaricose veins with competent distal veins. Even in the presence ofincompetent perforation, occlusion of the saphenofemoral junctionusually normalizes venous pressure.

The initial defect in secondary varicose veins is often incompetence ofa venous valve secondary to hypertension in the deep venous system.Since this increased pressure is manifested in the deep and perforatingveins, correction of one site of incompetence could clearly beinsufficient as other sites of incompetence will be prone to develop.However, repair of the deep vein valves would correct the deep venoushypertension and could potentially correct the secondary valve failure.Apart from the initial defect, the pathophysiology is similar to that ofvaricose veins.

Accordingly, methods of treating a venous valve related condition maycomprise the step of providing one or more medical devices comprisingimplantable frames as described herein. Methods of treatment maycomprise the step of providing one or more frames attached to one ormore valve leaflets. In some examples, methods of treatment may alsoinclude the steps of delivering a medical device to a point of treatmentin a body vessel, and deploying a medical device at the point oftreatment, where the medical devices are as described herein. Suchmedical devices can be inserted intravascularly, for example from animplantation catheter. The medical devices can function as a replacementvenous valve, or enhance venous valve function by bringing incompetentvalve leaflets into closer proximity. In one procedure, venous valvefunction can be provided by an implanted medical device.

FIG. 8 is a diagram of a human leg 400 showing certain venous structurestherein. In particular, shown is human leg 400 having GSV 410 andfemoral vein 411 which adjoin at the sapheno-femoral junction 412. Inaccordance with certain methods of treatment, a medical devicecomprising an implantable frame may be placed in the GSV 410 between apoint 413 occurring near the medial side of the knee and a point 414occurring prior to the sapheno-femoral junction 412. Desirably, themedical device functions as a valve to prevent or reduce reflux ofvenous blood from the sapheno-femoral junction 412 in a direction downtoward the medial side of the knee (e.g. at point 413). Such occlusionmay be effective to treat varicosities that commonly occur in lowerportions of the leg, e.g. portions occurring below the knee.

The medical device is preferably implanted from a delivery catheter viapercutaneous access to the GSV 410, for example by the Seldingertechnique or any other suitable technique. For instance, an accessneedle (not shown) can be passed through the skin to access the GSV 410,and a wire guide can be passed through the access needle and into thevein. Prior to deployment of an inverted occlusion device (not shown),wire guide can be used for any number of conventional proceduresincluding catheterization and imaging procedures in order to locate thesapheno-femoral junction. After any such preliminary procedures that areperformed, the wire guide can be used in a deployment procedure for aninflatable occlusion device.

Methods for delivering a medical device as described herein to anysuitable body vessel are also provided, such as a vein, artery, billiaryduct, ureteral vessel, body passage or portion of the alimentary canal.

While various aspects and examples have been described, it will beapparent to those of ordinary skill in the art that many more examplesand implementations are possible within the scope of the disclosure.Accordingly, the disclosure is not to be restricted except in light ofthe attached claims and their equivalents.

1. A medical device for implantation in a body vessel, comprising: animplantable frame comprising a surface and a plurality of projectionsextending from the surface; the plurality of projections comprising afirst projection including a beveled edge and having a cross-sectionalarea at the intersection of the first projection and the implantableframe surface that is less than about 10 mm²; and a biocompatibleremovable material enclosing the beveled edge of the first projection.2. The medical device of claim 1, where the biocompatible removablematerial is water-soluble.
 3. The medical device of claim 1, where thebiocompatible removable material encloses the first projection.
 4. Themedical device of claim 1, where the removable material enclosing thebeveled edge of the first projection is between about 1 μm and 1 mmthick.
 5. The medical device of claim 1, where the plurality ofprojections comprise a substantially triangular, substantially square,substantially rectangular, substantially elliptical, or substantiallysemi-circular cross-sectional shape at intersection of the firstprojection and the implantable frame surface the projection.
 6. Themedical device of claim 1, where the plurality of projections comprisebarbs configured to engage the wall of a body vessel.
 7. The medicaldevice of claim 1, where the plurality of projections comprise barbsenclosed by a biocompatible removable material.
 8. The medical device ofclaim 1, where the implantable frame has a tubular configuration that ismoveable from a radially compressed state to a radially expanded state.9. The medical device of claim 1, where the implantable frame comprisesa material selected from the group consisting of: a nickel-titaniumalloy, a cobalt-chromium alloy, and stainless steel.
 10. The medicaldevice of claim 1, the implantable frame further comprising a pluralityof struts and bends defining a substantially cylindrical lumen.
 11. Themedical device of claim 1, where the medical device is an implantablevalve further comprising at least one valve leaflet attached to theimplantable frame, the implantable frame comprising a plurality ofstruts and bends defining a substantially cylindrical lumen and having aplurality of projections configured as barbs attached to the implantableframe.
 12. A medical device for implantation in a body vessel,comprising: an implantable frame comprising a surface having at least afirst portion and a second portion; the first portion comprising atleast a first projection having a beveled edge; the second portionhaving no projections; and a biocompatible removable material enclosingat least the beveled edge of the first projection.
 13. The medicaldevice of claim 12, where the first projection intersects the surface ofthe implantable frame with a cross-sectional area that is less thanabout 10 mm²
 14. The medical device of claim 12, where the removablematerial has a thickness of between about 10 μm and 1 mm.
 15. Themedical device of claim 12, where the removable material is present onthe first portion of the frame with a thickness of between about 10 μmand about 1 mm and where the removable material is not coated on thesecond portion of the surface of the implantable frame
 16. The medicaldevice of claim 15, where the first portion of the surface of theimplantable frame has a surface area that is less than about 10 mm². 17.The medical device of claim 16, where the second portion of the surfaceof the implantable frame has a surface area that is at least about 1mm².
 18. The medical device of claim 12, the first portion furthercomprising a plurality of projections configured as barbs.
 19. A medicaldevice for implantation in a body vessel, comprising: an implantableframe comprising a plurality of struts and bends defining asubstantially cylindrical lumen and a surface having a first portion anda second portion the first portion comprising a plurality of barbsextending from the surface and the second portion having no barbs; theplurality of barbs having a cross-sectional area at the intersection ofthe barb and the implantable frame surface that is less than about 10mm²; a water-soluble biocompatible removable material enclosing at leastone of the plurality of barbs and having a thickness between about 10 μmand about 1 mm; and the second portion having no removable material. 20.The device of claim 20, where the plurality of barbs are individuallyenclosed be separate portions of the removable material